MECHANISM OF MICROTUBULE DYNAMICS REGULATION BY KINESINS

描述（由申请人提供）：运动蛋白是真核细胞骨架蛋白，以其运动活性而闻名，但它们也是微管（MT）动力学的重要调节剂，即MT聚合物生长或收缩的能力。本项目旨在建立微管（MT）动力学调节的分子机制的超家族成员的驱动蛋白。这些运动蛋白对MT动力学的调节在多种细胞过程中发挥重要作用，如有丝分裂、细胞分裂、神经发育和纤毛和中心粒长度的控制，但这些运动蛋白稳定或破坏MT的机制尚不完全清楚。我们将测试所有这些驱动蛋白通过改变微管蛋白的结构来影响mt动力学的一般假设，以支持或不支持微管蛋白间接触的形成

DESCRIPTION (provided by applicant): Kinesins are eukaryotic cytoskeletal proteins best known for their motile activity, but they are also important regulators of microtubule (MT) dynamics, the ability of the MT polymer to grow or shrink. This project seeks to establish the molecular mechanism of microtubule (MT) dynamics regulation by members of the kinesin superfamily. Regulation of MT dynamics by these kinesins play important roles in a variety of cell processes such as mitosis, cytokinesis, neural development and control of cilia and centriole length, but the mechanisms by which these kinesins stabilize or destabilize MTs are not fully clear. We will test the general hypothesis that all these kinesin affect MT-dynamics by modifying the structure of tubulin to favor or disfavor the formation of the inter-tubulin contacts that hold the MT polymer together. To address this hypothesis we will use electron microscopy and other approaches to determine the structure of tubulin complexes of three model kinesins. The proposal has two general aims. The fist aim is to establish the mechanism of MT depolymerization by the kinesins KLP10A and Kar3. The second aim addresses the mechanism of MT stabilization by the kinesin KIF14.